The study of human cells defective in repairing damaged DNA was extended, with the rationale that DNA repair-deficient cells are more susceptible to the adverse effects of carcinogens (cell killing, mutagenesis, sister chromatid exchange, and malignant transformation) than their repair-proficient counterparts. A group of 19 human tumor and eight SV40-transformed strains almost totally deficient in the repair of 0-6-methylguanine (0-6-MeG, a modified DNa base made by certain methylating agents) was identified earlier in this project. Such stains are called Mer-. Transformation by SV40, Rous sarcoma virus, adenovirus or Epstein-Barr virus produces Mer- strains. Mer+ but not Mer- stains contain about 60,000 copies of a 22,000 MW 0-6-MeG-DNA methyltransferase (06DMT) that is responsible for repairing 0-6-MeG by demethylation. Cell strains having intermediate amounts of 06DMT also have intermediate sensitivity to killing by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) or by 1-(2-chloroethylk)-1-notrosourea (CNU), and to the induction of sister chromatid exchanges of MNNG. Human interferons Alpha and Beta inactivate Mer- tumor strains while Mer+ human tumor strains are more resistant to such treatment, indicating an association between defective repair of 0-6-MeG and sensitivity to interferons. Oncogene activation was linked to depletion of 06DMT in mouse cells by a study in which interferon was used to produce revertants that failed to express the human c-Ha-ras 1 gene. Compared to non-transformed cells or revertant cells that did not express the oncogene, transformed cells that showed oncogene expression had reduced 06DMT and post-CNU survival levels. A study done to investigate the role of poly ADP ribose polymerase in lethality due to 0-6-MeG indicated no such association, However, poly ADP ribose polymerase is likely involved in the repair of 3- or 7-methylated adenines or guanines.